This application for an NIMH Mentored Patient-Oriented Career Development Award (K23), titled "Adherence to HCV Treatment in HCV and HCV/HIV Patients," seeks to develop the Principal Investigator (PI), a clinical psychologist, into an independent investigator performing research with nonadherent medically ill patients with comorbid psychiatric and substance use disorders. The short-term career goals of the PI include obtaining (1) knowledge of the diagnosis and treatment of HCV and HIV infections, (2) knowledge of the measurement of adherence and of the biological consequences of non-adherence, (3) training in substance abuse-related issues and neurocognitive aspects of HIV/HCV and substance abuse (4) training in research methodology, statistics, grant writing (5) training in public health and policy aspects of research on (former) injection drug users, (6) training in the conduct of ethical research, (7) training in the administration of structured psychiatric interview schedules. The long-term goals of the PI include conducting research on the impact of comorbid medical and psychiatric conditions on adherence to medical treatment, particularly with HCV and HCV/HIV patients. The research proposed is a prospective cohort study in which 100 HCV and 100 HCV/HIV patients will be enrolled just prior to initiating HCV therapy with pegylated IFN-alfa and ribavirin (PEG-IFN/RBV). Treatment with PEG-IFN/RBV is associated with numerous hematologic, physical, and neuropsychiatric side effects, which lead to high rates of early treatment discontinuation. The 200 recruited patients will be followed for the first 24 weeks of treatment to determine whether depression, neurocognitive functioning, substance abuse and treatment self-efficacy are associated with early treatment discontinuation in these two groups of patients and whether the two groups differ in rates of early treatment discontinuation. The findings of this study will have important implications for the development of interventions to support and assist HCV and HCV/HIV patients in completing their course of PEG-IFN/RBV treatment.